The long-term goals of the proposed research are directed at developing safe and efficacious recombinant avirulent Salmonella vaccines for oral administration to protect humans against bacterial, viral and mycotic pathogens, especially those that colonize on or invade into mucosal surfaces. Vaccines are also being constructed and evaluated (i) to immunize farm animals, especially poultry to prevent infection and colonization by human enteropathogens that are transmitted through the food chain to humans, (ii) to express hormones and or gamete-specific antigens to induce immune responses leading to sterilization or to block fertilization, (iii) to induce immune responses to tumor antigens or to kill tumor cells, and (iv) to augment and/or modulate the immune response expressed foreign antigens by co-expression of cytokines. Oral immunization with live Salmonella vaccines gives rise to the potential for fecal shedding with release to the environment of bacteria which could lead to immunization of individuals who did not elect to be vaccinated. There is also the possibility that farm animals that were sent to market too soon after immunization with these vaccines might lead to transmission of the vaccine strain through the food chain to humans. The objectives of the research proposed for the Phase II study are to continue to construct and evaluate strains with containment systems that lead to lysis or death within the immunized animal and that are unable to survive and proliferate in the environment. The strains will be tested for containment, avirulence and immunogenic attributes in vitro and after excretion. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE